Aromatic and heteroaromatic substructure are among the most important structural motifs abundant in organic molecules. The Friedel-Crafts alkylation [Olah, G. A. Friedel-crafts chemistry. Wiley New York: 1973], one of the oldest known chemical transformations, is the preferred method for introducing alkyl substituents, derived from alkyl halides, onto aromatic compounds [Rueping, M. et al. Org. Chem. 2010, 6, 6.]. Over the years, the classic methods have seen improvements and techniques that are less destructive, non-toxic and have higher selectivity [Mertins, K. et al, Angewandte Chemie International Edition 2005, 44, 238] were developed.
While this method is reliable for installation of benzyl groups and secondary and tertiary alkyl moieties [Sawama, Y. et al., Chemistry—A European Journal 2014, 20, 510], the major limitation of the reaction lies in the fact that it is unsuitable for primary alkyl halides. The latter react less readily, therefore require harsh conditions [Smith, M. B.; March, J., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley: 2007; Carey, F. A.; Sundberg, R. J., Advanced Organic Chemistry: Part A: Structure and Mechanisms. Springer: 2007], and result in a mixture of rearrangement products. Other major drawbacks, such as polyalkylation of the aromatic core, and the requirement for strict anhydrous conditions, further affect the applicability of the process. To overtake the synthetic difficulties of placing primary alkyl groups onto aromatic compounds, alternative multi-step protocols have been developed, such as Friedel-Crafts acylation and reduction, reductive Friedel-Crafts alkylation [suchimoto, T et al., Chemical Communications 1996, 2345], metal catalyzed cross-coupling [Hatakeyama, T. et al. J. Am. Chem. Soc. 2010, 132, 10674; González-Bobes, F., Fu, G. C. J. Am. Chem. Soc. 2006, 128, 5360; Molander, G. A. et al. Org. Lett. 2010, 12, 5783; Yang, C. T. et al., Angew. Chem. Int. Ed. 2011, 50, 3904. Li, C. et al, Angewandte Chemie International Edition 2015], and metal catalyzed C—H activation [Bair, J. S. et al., J. Am. Chem. Soc. 2014, 136, 13098; Robbins, D. W.; Hartwig, J. F. Angew. Chem. Int. Ed. 2013, 52, 933].